The central goal of this application is to further my development as a clinical investigator, while enhancing my opportunities to mentor fellows and promising young faculty interested in careers in clinical research. Patient-oriented clinical research has been the cornerstone of my medical career. My main research focus has been the investigation of primary hyperparathyroidism (PHPT). I have studied the clinical presentation of the disease;its natural history with and without surgery;medical treatment options;and malignant PHPT (parathyroid cancer). I plan to continue and expand my collaborative research program in PHPT. My hypothesis is that sufficiently sensitive techniques will detect sub-clinical features of PHPT that have up to now eluded detection, and that these features may regress with surgical cure. Having shown this to be true in the skeleton, the research in this proposal will investigate possible cardiovascular and neuropsychological abnormalities. The research will also characterize a non-classical presentation of PHPT with normal serum calcium levels;and will investigate the increase in bone density that follows parathyroidectomy. These projects should enhance our understanding of modern PHPT. In addition, given data supporting non-intervention in many patients with PHPT (NIH Surgical Guidelines, 2002), these studies could have major public health implications, leading to a new standard-of-care for the evaluation and management of PHPT. The projects will provide fertile training ground for mentoring young investigators in patient oriented research in the field of metabolic bone disease. I have had significant success as a mentor, with 11 current or past trainees, 2 with Endocrine Fellows Foundations grants, and one currently holding a K23/K30 Award. As Co-Director of our NIH Postdoctoral Fellowship Program, I have regular access to Endocrine Fellows, as well as residents, students and junior faculty interested in participating in my research. The environment at Columbia is outstanding, with a large and supportive Endocrine Division, and an NIH funded Clinical Research Center. However, without further support for my research and mentoring effors, I will have to increase my clinical and administrative responsibilities. The K24 mechanism will allow me to achieve my goals: continued productivity in the clinical investigation of parathyroid disease, with protected time for mentoring fellows and junior colleagues interested in patient oriented clinical research as a career path.